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Transplantation ; 100(12): e120-e127, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27861292

RESUMO

BACKGROUND: The development of safe and reliable protocols for the transplantation of the face and hands may be accomplished with animal modeling of transplantation of vascularized composite allografts (VCA). Previously, we demonstrated that tolerance to a VCA could be achieved after canine recipients were simultaneously given marrow from a dog leukocyte antigen-identical donor. In the present study, we extend those findings across a dog leukocyte antigen mismatched barrier. METHODS: Eight recipient dogs received total body irradiation (4.5 cGy), hematopoietic cell transplantation (HCT), either marrow (n = 4) or granulocyte-colony stimulating factor mobilized peripheral blood stem cells (n = 4), and a VCA transplant from the HCT donor. Post grafting immunosuppression consisted of mycophenolate mofetil (28 days) and cyclosporine (35 days). RESULTS: In 4 dogs receiving bone marrow, 1 accepted both its marrow transplant and demonstrated long-term tolerance to the donor VCA (>52 weeks). Three dogs rejected both their marrow transplants and VCA at 5 to 7 weeks posttransplant. Dogs receiving mobilized stem cells all accepted their stem cell transplant and became tolerant to the VCA. However, 3 dogs developed graft-versus-host disease, whereas 1 dog rejected its stem cell graft by week 15 but exhibited long-term tolerance toward its VCA (>90 weeks). CONCLUSIONS: The data suggest that simultaneous transplantation of mobilized stem cells and a VCA is feasible and leads to tolerance toward the VCA in a haploidentical setting. However, there is a higher rate of donor stem cell engraftment compared with marrow HCT and an increase in the incidence of graft-versus-host disease.


Assuntos
Células da Medula Óssea/metabolismo , Aloenxertos Compostos/imunologia , Sobrevivência de Enxerto , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas , Animais , Antígenos/química , Ciclosporina/farmacologia , Cães , Rejeição de Enxerto/imunologia , Doença Enxerto-Hospedeiro , Fator Estimulador de Colônias de Granulócitos/farmacologia , Terapia de Imunossupressão , Leucócitos/imunologia , Ácido Micofenólico/farmacologia , Reprodutibilidade dos Testes , Transplante de Pele , Condicionamento Pré-Transplante , Tolerância ao Transplante , Transplante Homólogo
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